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The spine apparatus is an essential component of dendritic spines of cortical and hippocampal neurons, yet its functions are still enigmatic. Synaptopodin (SP), an actin-binding protein, is tightly associated with the spine apparatus and it may play a role in synaptic plasticity, but it has not yet been linked mechanistically to synaptic functions. We(More)
UNLABELLED Hypoxia-inducible factors (HIFs) provoke adaptation to hypoxic stress occurring in rapidly growing tumor tissues. Therefore, overexpression of HIF-1 or HIF-2 is a common feature in hepatocellular carcinoma but their specific function is still controversially discussed. To analyze HIF function in hypoxia-induced cell death we created a stable(More)
The amyloid precursor protein (APP) has been suggested to regulate gene expression. GeneChip analysis and in vitro kinase assays revealed potent APP-dependent repression of c-Jun, its target gene SPARC and reduced basal c-Jun N-terminal kinase (JNK) activity in PC12 cells overexpressing APP. UV-induced activation of the JNK signalling pathway and subsequent(More)
Impaired proteasomal function is a major hallmark in the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD). Here we investigated the biological properties of the secreted cleavage product of APP (sAPPalpha) in antagonizing stress signalling, dendritic degeneration and neuronal cell death induced by the proteasome inhibitor(More)
Alzheimer's disease (AD) is characterized by the pathological deposition of amyloid-beta protein in the aged brain. Inefficient clearance of amyloid-beta from brain tissue is believed to play a major role in the pathogenesis of these deposits. Since amyloid-beta clearance likely involves activation of microglial cells via toll-like receptors and since these(More)
Gradual changes in steady-state levels of beta amyloid peptides (Abeta) in brain are considered an initial step in the amyloid cascade hypothesis of Alzheimer's disease. Abeta is a product of the secretase cleavage of amyloid precursor protein (APP). There is evidence that the membrane lipid environment may modulate secretase activity and alters its(More)
The fluidity of neuronal membranes plays a pivotal role in brain aging and neurodegeneration. In this study, we investigated the role of the omega-3 fatty acid docosahexaenoic acid (DHA) in modulation of membrane fluidity, APP processing, and protection from cytotoxic stress. To this end, we applied unilamellar transfer liposomes, which provided protection(More)
Vascular endothelial growth factor receptor 1 (VEGFR-1) is highly expressed in endothelial cells and regulates developmental angiogenesis by acting as a decoy receptor and trapping VEGF-A. Vascular endothelial growth factor receptor 1 is also expressed in monocytes and macrophages; mice lacking the VEGFR-1 tyrosine kinase (TK) domain (VEGFR-1 TK mice)(More)
BACKGROUND Diffuse infiltration remains the fulcrum of glioblastoma's incurability, leading inevitably to recurrence. Therefore, uncovering the pathological mechanism is imperative. Because signal transducer and activator of transcription 3 (STAT3) correlates with glioma malignancy and predicts poor clinical outcome, we determined its role in glioma single(More)
Here we investigated the role of the amyloid precursor protein (APP) in regulation of Ca(2+) store depletion-induced neural cell death. Ca(2+) store depletion from the endoplasmic reticulum (ER) was induced by the SERCA (Sarco/Endoplasmic Reticulum Calcium ATPase) inhibitor thapsigargin which led to a rapid induction of the unfolded protein response (UPR)(More)